Harold C. Simmons Cancer Center Experimental Therapeutics of Cancer Scientific Program Project Summary/Abstract The Experimental Therapeutics (ET) Program brings together 44 full Simmons Cancer Center (SCC) members, including 13 from basic science departments and 31 from clinical departments, to develop novel therapeutic strategies and to evaluate these approaches by conducting investigator-initiated clinical trials. The program has 27 NCI projects, a lung cancer SPORE, as well as 12 multi-investigator awards. ET Program clinical investigators represent key oncology disciplines, including medical, surgical, pediatrics, and radiation oncology; radiology; and pathology. Investigators in the ET Program are currently supported by over $24.7 million in peer-reviewed funding (total costs) with $7.5 million from the NCI, $4 million from other NIH sources, and $7.3 million from the Cancer Prevention and Research Institute of Texas (CPRIT) The ET Program is designed to provide an organized, science-based conduit for translating SCC discoveries from the scientific programs to the clinic, and to help establish appropriate preclinical models and data to facilitate clinical translation. Likewise, clinical data are then used to form new hypotheses tested by our strong basic science foundation throughout the SCC. The program themes focus on drug (Themes 1,2) and biomarker (Themes 3,4) discovery to identify optimal populations for these new treatments. Theme 1: Molecular Therapeutic Sensitizers Theme 2: Tumor Microenvironment and Protein Therapy Theme 3: Imaging and Drug Delivery Theme 4: Cancer Vulnerabilities The Co-Leaders of the ET Program work together to foster and develop themes, goals, membership, and new collaborations in specific research areas for clinical translation. This process heavily engages SCC disease DOTs (disease oriented teams) to focus specific therapeutics on select cancers, as evidenced by mechanistic- based research where target validation is assessed using pharmacodynamic biomarkers. These activities, in turn, stimulate intra- and inter-programmatic collaborations. The ET Program averages over 100 publications per year, and since 2009 the level of collaborative publications has remained quite high, with 35% intra- programmatic, 34% inter-programmatic and 28% inter-institutional with authors in other NCI-designated cancer centers.